Adherent cells have conventionally been grown on glass surfaces or on polymer substrates. Surfaces for cell culture are often pre-treated to enhance cell adhesion and proliferation. A wide variety of static culture vessels is available for adherent cell culture in the laboratory. While static culture vessels such as tissue culture flask or multi-layer cell growth flasks do allow for some scale-up of adherent cell culture, they become limiting at larger scales as they are labor-intensive, subject to variability due to manual processing, and limited in volumetric productivity (e.g. cell yield per volume of incubator space).
Cell culture using bioreactors has long been practiced as the preferred scale-up method for cell culture. The use of microcarriers for adherent cell culture is common in industrial practice, such as in bioprocessing. Microcarrier beads, or planar carriers have been developed to provide increased surface area for cell attachment, and to enable high-density adherent cell culture on an industrial scale.
Typical bioreactor vessels employ some means of agitation, such as internal impellers, rocking or shaking mechanisms to suspend the cells and allow mass transfer of nutrients, oxygen and metabolic waste products. Conventional carriers can be prone to sticking to the walls of reactors and other surfaces; also, planar carriers can be prone to stacking/clumping as cell growth proceeds, particularly when the agitation in the bioreactor is intermittent rather than continuous. This can affect cell growth and nutrient/metabolite transport as well as cell release.
Therefore, there is a need for a carrier for adherent cell growth that avoids clumping of carriers to each other or sticking of carriers to the wall/other surfaces of the reactor, so that it facilitates uninterrupted cell expansion, visualization, and release. Efficient cell expansion is particularly important for high yield industrial scale cell culture processes for adherent cells, including such shear-sensitive cells as mesenchymal stromal cells (MSCs), which are currently expanded in static culture vessels. Therefore, the development of cell culture carriers that facilitate cell attachment, proliferation and release, and that reduce stacking and sticking of the carriers is highly desirable.